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Oxa-Michael-based divergent synthesis of artificial glutamate analogs.

ABSTRACT: Herein we report stereoselective generation of two skeletons, 1,3-dioxane and tetrahydropyranol, by oxa-Michael reaction as the key reaction from δ-hydroxyenone. The construction of the 1,3-dioxane skeleton, achieved through hemiacetal formation followed by oxa-Michael reaction from δ-hydroxyenone, was exploited to access structurally diverse heterotricyclic artificial glutamate analogs. On the other hand, formation of a novel tetrahydro-2H-pyranol skeleton was accomplished by the inverse reaction order: oxa-Michael reaction followed by hemiacetal formation. Thus, this study succeeded in showing that structural diversity in a compound collection can be acquired by interchanging the order of just two reactions. Among the skeletally diverse, heterotricyclic artificial glutamate analogs synthesized in this study, a neuronally active compound named TKM-50 was discovered in the mice in vivo assay.

SUBMITTER: Tsukamoto S

PROVIDER: S-EPMC9364357 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Oxa-Michael-based divergent synthesis of artificial glutamate analogs.

Tsukamoto Shuntaro S Hlokoane Oriel O Miyako Kei K Irie Raku R Sakai Ryuichi R Oikawa Masato M

RSC advances 20220810 34

Herein we report stereoselective generation of two skeletons, 1,3-dioxane and tetrahydropyranol, by oxa-Michael reaction as the key reaction from δ-hydroxyenone. The construction of the 1,3-dioxane skeleton, achieved through hemiacetal formation followed by oxa-Michael reaction from δ-hydroxyenone, was exploited to access structurally diverse heterotricyclic artificial glutamate analogs. On the other hand, formation of a novel tetrahydro-2H-pyranol skeleton was accomplished by the inverse ...[more]

PMID: 36043066

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